Chagas' disease or South American trypanosomiasis, caused by the monocellular flagellate Trypanosoma cruzi, represents a major health problem in South and Central America; cases have been occasionally reported in the United States. Experimental research dealing with this problem has made frequent use of either culture or host forms of T. cruzi. However, virtually no information is available on host interactions with and mechanisms of defense against the vector-transmitted metacyclic forms of T. cruzi which cause Chagas' disease in nature. The proposed research plan takes advantage of an uncommon combination of facilities and expertise in the areas of immunology, entomology and parasitology and is directed toward: 1. Defining the sensitivity of vector-transmissible metacyclic T. cruzi to immunologic mechanisms of parasite destruction such as antibody-dependent complement-mediated lysis and antibody-dependent cell-mediated cytotoxicity. The requirements for production of these reactions will also be studied. 2. Establishing if there is immunologic cross-reactivity between culture epimastigotes or mammalian trypomastigotes and vector metacyclic forms of T. cruzi through a series of experimental approaches involving fluorescent antibody techniques, immune lysis, micro-agglutination, quantitative cross-absorption, etc. This subject is relevant to the potential use of antigens derived from forms of T. cruzi that can be readily obtained in large quantities for vaccination against natural infection with this parasite. 3. Studying cross-protection against infection with metacyclic forms of T. cruzi by either immunization with or passive transfers of antibodies raised against culture or mammalian trypomastigote forms .